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Leuk Res. 2013 Nov;37(11):1461-7. doi: 10.1016/j.leukres.2013.07.034. Epub 2013 Aug 6.

Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.

Author information

1
Departments of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX, USA.

Abstract

Akt, a serine/threonine protein kinase, is constitutively phosphorylated and hyperactivated in multiple cancers, including acute myeloid leukemia. High levels are linked to poor survival and inferior responses to chemotherapy, making Akt inhibition an attractive therapeutic target. In this phase I/II study of TCN-PM, a small-molecule Akt inhibitor, TCN-PM therapy was well tolerated in patients with advanced hematological malignancies, and reduced levels of phosphorylation of Akt and its substrate Bad were shown, consistent with inhibition of this survival pathway and induction of cell death. Further investigation of TCN-PM alone or in combination in patients with high Akt levels is warranted.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00642031.

KEYWORDS:

AML; Akt; Nucleoside analog; Phase I clinical trial; Triciribine

PMID:
23993427
PMCID:
PMC4205589
DOI:
10.1016/j.leukres.2013.07.034
[Indexed for MEDLINE]
Free PMC Article

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